Chidamide with reduced-dose R-mini CHOP followed by chidamide plus CD20 antibody maintenance for elderly MYC/BCL2 double-expressor DLBCL

A Phase II, Open-label, Single-arm Clinical Study of Chidamide in Combination With the R-mini CHOP Regimen, Followed by Chidamide Plus CD20 as Maintenance Therapy, in Elderly Patients With Newly Diagnosed MYC/BCL2 Co-expressor DLBCL

This trial tests whether adding chidamide to reduced-dose R-mini CHOP, followed by chidamide plus a CD20 antibody, helps people aged 70 and older with newly diagnosed MYC/BCL2 double-expressor DLBCL live longer without disease progression.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 70 Years and up
• Sex: All
• Sponsor: The First Hospital of Jilin University (Academic / other)
• Drugs / interventions: rituximab
• Locations: 1 site (Changchun, Jilin)
• Trial ID: NCT07493148 on ClinicalTrials.gov

What this trial studies

This Phase 2, single-center interventional study gives patients aged 70 or older an induction regimen of chidamide combined with R-mini CHOP followed by maintenance with chidamide plus a CD20 monoclonal antibody (rituximab). The primary endpoint is 2-year progression-free survival. Secondary endpoints include objective response rate, complete response rate, duration of response, conversion from PR/SD to CR/PR, overall survival, and safety. Exploratory analyses will examine correlations between tumor genomics, proteomics, circulating tumor DNA, and treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates are people aged 70 or older with newly diagnosed CD20-positive DLBCL that meets MYC ≥40% and BCL2 ≥50% double-expressor by IHC, is not double‑hit or triple‑hit, has ECOG 0–2, IPI >1, and at least one FDG-avid lesion on PET-CT.

Not a fit: Patients younger than 70, those with prior DLBCL treatment, double‑hit or triple‑hit lymphoma, or poor performance status or significant organ dysfunction are unlikely to benefit from or be eligible for this protocol.

Why it matters

Potential benefit: If successful, this approach could improve progression-free survival and durable remissions in older patients who cannot tolerate full-dose R-CHOP.

How similar studies have performed: HDAC inhibitors such as chidamide have limited prior data in DLBCL and combining them with R-CHOP is exploratory, with some early-phase signals but no definitive proof of benefit so far.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 70 years;
2. No prior treatment for DLBCL;
3. Histopathologically confirmed diagnosis (all of the following conditions must be met simultaneously): ① Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), and CD20-positive; ② "MYC/BCL2 double-expressor": Immunohistochemistry (IHC) per WHO criteria: MYC ≥ 40%, and BCL2 ≥ 50%; ③ Non-"double-hit" or "triple-hit" lymphoma;
4. At least one 18F-fluorodeoxyglucose (18FDG)-avid lesion on positron emission tomography-computed tomography (PET-CT) according to the 2014 Lugano classification for Hodgkin and non-Hodgkin lymphoma;
5. International Prognostic Index (IPI) score \> 1;
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2;
7. At screening, laboratory tests must meet the following criteria, unless judged by the investigator to be due to lymphoma (no corrective or supportive treatment for the indicators below within 2 weeks prior to assessment): ① Hematology: Hemoglobin (Hb) ≥ 90 g/L, Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, Platelet count (PLT) ≥ 90 × 10⁹/L; ② Biochemistry: Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN); Total bilirubin (TBIL) ≤ 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN in cases of liver metastasis);
8. Life expectancy ≥ 6 months;
9. Understand and voluntarily sign a written informed consent form.

Exclusion Criteria:

1. Central nervous system (CNS) involvement;
2. Transformed lymphoma, i.e., lymphoma transformed from other lymphoma types such as follicular lymphoma, marginal zone B-cell lymphoma, or chronic lymphocytic leukemia/small lymphocytic lymphoma; specific subtypes of DLBCL (e.g., primary CNS DLBCL, etc.);
3. Uncontrolled cardiovascular or cerebrovascular diseases, coagulation disorders, autoimmune diseases, or severe infectious diseases;
4. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergic reactions to murine products; contraindications to any component of the CHOP regimen or chidamide;
5. HIV/HCV infection;
6. If HBsAg is positive, HBV DNA testing is required; patients with negative DNA may be enrolled. If HBsAg is negative but HBcAb is positive (regardless of HBsAb status), HBV DNA testing is required; patients with negative DNA may be enrolled.
7. Uncontrolled cardiovascular or cerebrovascular diseases, coagulation disorders, autoimmune diseases, or severe infectious diseases;
8. Inability to comply with the study protocol due to psychiatric or other unknown reasons;
9. For female patients of childbearing potential or male patients with partners of childbearing potential, unwillingness or inability to use effective contraception throughout the study treatment period and for 12 weeks after the last dose of chidamide or 12 months after the last dose of rituximab, whichever is longer; pregnant or breastfeeding women;
10. Other conditions deemed unsuitable for participation in this trial.

Where this trial is running

Changchun, Jilin

• The First Bethune Hospital of Jilin University — Changchun, Jilin, China (Recruiting)

Study contacts

• Principal investigator: Ou Bai, PHD — The First Bethune Hospital of Jilin University
• Study coordinator: Ou Bai, PHD

Conditions Diffuse Large B-Cell Lymphoma; newly diagnosed MYC/BCL2 double-expressor DLBCL